Clinical and molecular significance of homologous recombination deficiency positive non-small cell lung cancer in Chinese population: An integrated genomic and transcriptional analysis

• DOI: 10.21147/j.issn.1000-9604.2024.03.05
• Publication Date: 2025-05-30T02:48:04Z
• Authors: Yifei Wang; ; Yidan Ma; Lei He; Jun Du; Xiaoguang Li; Peng Jiao; Xiaonan Wu; Xiaomao Xu; Wei Zhou; Li Yang; Jing Di; Changbin Zhu; Liming Xu; Tianlin Sun; Lin Li; Dongge Liu; Zheng Wang
• Keywords: Chinese population

The clinical significance of homologous recombination deficiency (HRD) in breast cancer, ovarian and prostate cancer has been established, but the value HRD non-small cell lung (NSCLC) not fully investigated. This study aimed to systematically analyze status untreated NSCLC its relationship with patient prognosis further guide care. A total 355 treatment-naïve patients were retrospectively enrolled. was assessed using AmoyDx Genomic Scar Score (GSS), a score ≥50 considered HRD-positive. Genomic, transcriptomic, tumor microenvironmental characteristics between HRD-positive HRD-negative analyzed. Of patients, 25.1% (89/355) Compared had more somatic pathogenic repair (HRR) mutations, higher mutation burden (TMB) (P<0.001), fewer driver gene mutations (P<0.001). Furthermore, amplifications PI3K pathway cycle genes, MET MYC epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) mutant NSCLC, PIK3CA AURKA EGFR/ALK wild-type NSCLC. displayed proliferation immunosuppression activity. showed activated signatures major histocompatibility complex (MHC)-II, interferon (IFN)-γ effector memory CD8+ T cells. worse shorter progression-free survival (PFS) targeted therapy (first- third-generation EGFR-TKIs) (P=0.042). Additionally, HRD-positive, numerically lower response platinum-free immunotherapy regimens. Unique genomic transcriptional found Poor poor EGFR-TKIs observed highlights potential actionable alterations suggesting possible combinational therapeutic strategies for these patients.